Moxifloxacin Hydrochloride chemically known as 1-cyclopropyl-7-[S,S]-2,8-diazabicyclo-[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline carboxylic acid hydrochloride is a synthetic fluoroquinoline broad spectrum antibacterial particularly against Gram-positive bacteria and is known from EP 350,733 and EP 550,903 with following chemical structure.

Moxifloxacin has activity against Gram-negative and Gram-positive microorganisms, including Streptococus pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenza, Haemophilus parainfluenzae and Moraxella catarrhalis and the activity shown to be unaffected by β-lactamases. Moxifloxacin is used to treat number of infections including endocarditis meningitis, tuberculosis, respiratory tract infections, anthrax and cellulitis.
US Application 20060264635 discloses process for the preparation of Moxifloxacin hydrochloride by using intermediate (4aS-Cis)-(1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(acyloxy-O)borate. The disclosure further refers to the preparation of above said intermediate by condensing dried (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(acyloxy-O)borate with (S,S)-2,8-diazabicyclo[4.3.0]nonane in solvents like Dimethyl sulfoxide (DMSO), Dimethyl formamide (DMF), Acetonitrile (ACN) or ethanol and base under heating conditions, which is then hydrolysed to get Moxifloxacin hydrochloride pseudohydrate followed by conversion to Moxifloxacin hydrochloride monohydrate by treating with HCl in ethanol.
The major drawback of the above mentioned process is that multiple isolation steps are required to get desired Moxifloxacin hydrochloride monohydrate, which ultimately results into increase in production cost.
PCT Application WO2008059223 discloses the process for the preparation of Moxifloxacin hydrochloride by condensing dried mass of (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(propyloxy-O)borate with (S,S)-2,8-diazabicyclo[4.3.0]nonane in an organic solvent such as Acetonitrile (ACN) or n-butanol at higher temperatures to obtain intermediate (4aS-Cis)-(1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(propyloxy-O)borate which is then hydrolysed using Hydrochloric acid (HCl) in methanol to get Moxifloxacin hydrochloride. Above mentioned process further refers the isolation of Moxifloxacin hydrochloride through acid base treatment which is being performed twice to get ‘C’ form of Moxifloxacin hydrochloride.
Here, condensation reaction requires higher temperature conditions which lead to the degradation of the compound and hence decreases the overall yield of the process. Moreover, there is involved an extra step of acid base treatment making process lengthy and unsuitable to employ at industrial scale.
The European Patent No's EP 350,733; EP 550,903 and EP 657,448 disclose the preparation of moxifloxacin hydrochloride involving the condensation of dried 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid or its esters with (S,S)-2,8-diazabicyclo[4.3.0]nonane in presence of base and its conversion to hydrochloride at higher temperatures leading to the formation of desired moxifloxacin along with its positional isomer namely 1-cyclopropyl-6-[S,S]-2,8-diazabicyclo-[4.3.0]non-8-yl)-7-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline carboxylic acid of Formula I-A as a major impurity.

The separation of side impurities and positional isomer in above said process entails tedious purification processes which results into lower yields thereby increasing cost of production.
U.S. Pat. No. 5,157,117 discloses (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(acyloxy-O)borate and process of its preparation by reacting ethyl-1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylate with boric acid and acetic anhydride in presence of zinc chloride and its conversion to Moxifloxacin hydrochloride.
The known forms of Moxifloxacin hydrochloride are the anhydrous and monohydrate. U.S. Pat. No. 5,849,752 discloses the monohydrate of Moxifloxacin hydrochloride and its preparation by treating the anhydrous crystalline form with ethanol/water mixture.
PCT Application WO2010052726 discloses preparation of Moxifloxacin hydrochloride by condensing dried mass of (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(acyloxy-O)borate with (S,S)-2,8-diazabicyclo[4.3.0]nonane in presence of solvent like toluene and base at reflux conditions. Similarly, Chinese Patent No. CN 102,276,603 discloses preparation of Moxifloxacin hydrochloride using dried mass of acyloxy boron complex and condensing it with (S,S)-2,8-diazabicyclo[4.3.0]nonane in presence of solvent like Acetonitrile (ACN) and base at reflux conditions.
The drawback of above said process is that condensation reaction is performed at reflux conditions which results into decomposition of boron complex, (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(acyloxy-O)borate resulting into formation of unwanted side products and hence loss in the overall yield.
Indian Patent No. IN 2010DE00518 discloses the preparation of Moxifloxacin hydrochloride by condensing boron complex, (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(acyloxy-O)borate with (S,S)-2,8-diazabicyclo[4.3.0]nonane in water using organic base at 45-50° C.
It is observed that the isolated Moxifloxacin hydrochloride is not of desired purity. To get Moxifloxacin hydrochloride of pharmacopeial grade, further crystallization in methanol and water is required. However the further purification results into massive loss in the yield of the desired product making process unsuitable at commercial scale production.
Chinese Patent No. CN 102,617,622 reveals preparation of moxifloxacin hydrochloride by condensing dried (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(acyloxy-O)borate with (S,S)-2,8-diazabicyclo[4.3.0]nonane in Acetonitrile (ACN) using Triethyl amine (TEA) as a base at room temperature.
In the prior art, the acyloxy borate complex namely (1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4)bis(acyloxy-O)borate is firstly dried under thermal conditions before using it for the condensation reaction. It is being observed that the acyloxy borate complex is thermally unstable compound and drying of the same requires critical parameters which are difficult to maintain at plant scale. Also, the drying of acyloxy boron compound is time consuming process, requiring approximately 24-32 hours of constant heating.
The processes disclosed in the prior art involve not only time-consuming steps but also multiple isolations, tedious work-ups and time-consuming purification processes, which results into wastage of material, thus making process lengthy, low yielding and uneconomical at commercial scale production.
Therefore, it is long felt need of the industry to provide high yielding and cost effective processes for the production of Moxifloxacin hydrochloride.